Induction of innate immune response through TLR2 and dectin 1 prevents type 1 diabetes.
Induction of innate immune response through TLR2 and dectin 1 prevents type 1 diabetes.
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DOI：
10.4049/jimmunol.181.12.8323
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Vasu C
中科院分区：
文献类型：
--
作者：
Karumuthil-Melethil S;Perez N;Li R;Vasu C
Studies have suggested a correlation between the decline in infectious diseases and increase in the incidence of T1D in developed countries. Pathogens influence the disease outcome through innate immune receptors such as toll-like receptors (TLRs). Here, we report the effect of ligation of TLR2 and dectin 1 on APCs, and the influence of innate immune response induced through these receptors on T1D. Exposure of APCs of non-obese diabetic (NOD) mice to zymosan, a fungal cell-wall component that is known to interact with TLR2 and dectin 1, resulted in the release of significant amounts of IL-10, TGF-β1, IL-2, and TNF-α. Treatment of pre- and early-hyperglycemic mice with zymosan resulted in suppression of insulitis leading to a significant delay in hyperglycemia. Importantly, T cells from zymosan treated mice showed reduced ability to induce diabetes in NOD-Scid mice compared to control T cells. Zymosan treatment induced suppression of T1D was associated with an increase in the CD62Lhigh T cell frequencies and enhanced suppressor function of CD4+CD25+ Tregs. Further, activation by anti-CD3-Ab induced larger amounts of TGF-β1 and/or IL-10 production by CD4+CD25+ and CD4+CD25- T cells from zymosan treated mice. These results show that innate immune response through TLR2 and dectin 1 results in suppressor cytokine production by APCs, and promotes regulatory function of T cells. Our study demonstrates the possible involvement of signaling through innate immune receptors such as TLR2 and dectin 1 in reduced T1D incidence under the conditions of low hygiene, and the potential of targeting them for treating T1D.
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